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Smallpox vaccination (vaccinia) is a generally safe and effective means to prevent smallpox. However, in a number of individuals, smallpox vaccination can result in untoward effects and adverse reactions. The majority of adverse reactions caused by the smallpox vaccine are mild to moderate complications that resolve on their own. Serious reactions are rare, but can be fatal.

There are two medications that may help persons who have certain serious reactions to the smallpox vaccine; vaccinia immune globulin (VIG) and cidofovir. VIG has been extensively used in the past and felt (but not shown in controlled studies) to be effective. Cidofovir may be effective based on studies in animals. Treatment with these medications may require the vaccine recipient to be in the hospital. Cidofovir is investigational and may cause a number of serious side effects itself.

Vaccinia
Immune Globulin (VIG)

VIG was originally produced in the 1960s from plasma obtained from recently vaccinated donors. It contained a high titer of anti-vaccinia neutralizing antibody. Because it contained a high proportion of aggregated protein it was administered solely by the intramuscular route and could not be used intravenously.

New lots of VIG have since been produced that meet the standards for intravenous immune globulin. This IV-VIG has new recommendations for both dosage and preferred method of administration. The new IV-VIG has a low level of aggregated protein, allowing it to be used by either the IM or IV route. Intravenous VIG will be most likely administered at a lower dose than the intramuscular preparation.

Concomitant
Use of VIG with Vaccination

In some instances, VIG was given concomitantly with vaccination to “prevent” complications in a susceptible person. Not enough is known about the efficacy of this practice to recommend its use. Furthermore, there is currently an insufficient amount of VIG to use prophylactically when the benefits are uncertain.

Dosage

For the treatment of severe complications of vaccinia vaccination, Vaccinia Immune Globulin Intravenous (Human) (VIGIV) should be administered at a dose of 6000 U/kg, as soon as symptoms appear and are judged to be due to severe vaccinia-related complication. Consideration may be given to repeat dosing, depending on the severity of the symptoms and response to treatment; however, clinical data on repeat doses are lacking.

The administration of higher doses (e.g. 9000 U/kg) may be considered in the event that the patient does not respond to the initial 6000 U/kg dose.

Frequency
of Use

Data from a CDC survey indicates that VIG was administered at a rate of 47 uses per 1 million primary vaccinees and 2 uses per million revaccinees.

Cidofovir

Another drug that may be used to treat certain serious smallpox vaccine
reactions is cidofovir, an antiviral drug marketed as Vistide®.

Cidofovir is currently licensed for the treatment of CMV retinitis and has demonstrated antiviral activity against poxviruses in vitro, and against cowpox and vaccinia viruses in mice.

HHowever, its use for the treatment of vaccinia adverse reactions is restricted under an Investigational New Drug (IND) protocol. According to the IND protocol, cidofovir would only be used when VIG was not efficacious. Healthcare providers considering use of cidofovir for the treatment of vaccinia adverse reactions should consult with HHS/CDC.

Renal toxicity is a known adverse reaction of cidofovir. Cidifovir may be administered with probenecid to mitigate renal damage.

Obtaining
VIG and Cidofovir

Indications for VIG/cidofovir release

Vaccinia Immune Globulin (VIG) is indicated for the treatment of certain serious smallpox vaccine adverse events, including progressive vaccinia, eczema vaccinatum, severe generalized vaccinia, vaccinia infection in individuals with certain skin conditions, and accidental implantation (if judged to be severe due to the number of lesions, toxicity of affected individual, or location). VIG is recommended as the first line of therapy. Cidofovir may be considered as a secondary treatment in consultation with HHS/CDC.

VIG and cidofovir are available for civilians through the CDC. Cidofovir provided by CDC can only be used under Investigational New Drug (IND) protocol for treatment of specific smallpox vaccine reactions. Based on the anticipated number of adverse events resulting from the planned vaccination program for healthcare workers, CDC’s supply of VIG should be adequate.

Process
for obtaining VIG/cidofovir under Investigational New Drug Protocol (IND)

Physicians should first contact their State Health Department when seeking consultation for civilian patients experiencing a severe or unexpected adverse event following smallpox vaccination or when requesting VIG or cidofovir. If further consultation is required, or VIG or cidofovir is recommended, the physician and State Health Department can request consultation through the CDC Director’s Emergency Operations Center .

According to FDA regulations, cidofovir released from the CDC must be administered according to their investigational new drug protocols (IND). The IND mandates that the treating physician must become a co-investigator. The responsibilities of the co-investigator are primarily to complete follow-up forms describing the clinical status of the patient being treated with cidofovir, including the prompt report of any significant adverse reaction in the recipient. Detailed information on the requirements of the IND will be shipped with the products.

Shipment
of VIG/cidofovir

VIG/cidofovir
will be shipped by the Strategic National Stockpile (SNS). The
CDC Smallpox Vaccine Adverse Events Clinical Consultation Team will
coordinate the shipment of VIG/cidofovir with SNS. The cost of VIG and
cidofovir and the cost of shipping will be covered by the U.S. Government.
Arrival of shipments should be expected within 12 hours of the approval
for release.